Thiotepa, Fludarabine, and Busulfan Conditioning Regimen before T Cell-Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Acute Myeloid Leukemia: A Bicentric Experience of 100 Patients

Biol Blood Marrow Transplant. 2019 Sep;25(9):1803-1809. doi: 10.1016/j.bbmt.2019.05.014. Epub 2019 May 22.

Abstract

Haploidentical stem cell transplantation (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) is an alternative treatment for acute myeloid leukemia (AML) patients who lack HLA-matched donors. Relapse after haplo-SCT remains a major concern, especially after nonmyeloablative conditioning regimens. Promising results were reported for TBF-based conditioning regimens (thiotepa, busulfan, and fludarabine) in patients transplanted from different categories of donors and for various disease types but not specifically in PT-Cy haplo-SCT for AML. Here we evaluate the outcome of 100 AML patients who received haplo-SCT with PT-Cy after TBF conditioning regimens (reduced-intensity conditioning, n = 77; myeloablative conditioning, n = 23) in 2 transplant programs. Cumulative incidences of grades III to IV acute and moderate or severe chronic graft-versus-host disease (GVHD) were 7% and 14%, respectively. NRM at 2 years was 28%, significantly influenced by disease status at haplo-SCT (first complete response [CR1] versus advanced AML: 16% versus 38%, P = .016) but not by conditioning intensity or age. The cumulative incidences of relapse at 2 years were 17% and 24% in CR1 and advanced AML, respectively (not significant). Progression-free survival, overall survival, and GVHD and relapse-free survival at 2 years were 67%, 71%, and 49% in CR1 patients, respectively, whereas comparative values in patients with advanced disease were 37%, 41%, and 32%. Our study suggests that TBF conditioning for PT-Cy haplo-SCT is safe and effective for AML patients in CR1. In patients with more advanced disease, the relatively low incidence of relapse seems counterbalanced by a high nonrelapse mortality, underlining the need for alternative strategies to decrease relapse risk, without increasing the intensity of conditioning regimen.

Keywords: AML; Haploidentical SCT; Thiotepa-busulfan-fludarabine.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Allografts
  • Busulfan / administration & dosage*
  • Chronic Disease
  • Cyclophosphamide / administration & dosage*
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease* / mortality
  • Graft vs Host Disease* / prevention & control
  • Humans
  • Leukemia, Myeloid, Acute* / mortality
  • Leukemia, Myeloid, Acute* / therapy
  • Male
  • Middle Aged
  • Stem Cell Transplantation*
  • Survival Rate
  • T-Lymphocytes*
  • Thiotepa / administration & dosage*
  • Transplantation Conditioning*
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives*

Substances

  • Cyclophosphamide
  • Thiotepa
  • Vidarabine
  • Busulfan
  • fludarabine